A7 Schizophrenia (dopaminergic and glutamatergic hypothesis)

Title

The model integrates the two main neurochemical hypotheses of schizophrenia: dopaminergic hyperactivity in the mesolimbic pathway, associated with positive symptoms, and dopaminergic hypoactivity in the mesocortical pathway, associated with negative and cognitive symptoms. Underlying both, the hypofunction of NMDA receptors (direct extension of the receptor-ligand kinetics of E10) reduces the excitation of cortical GABAergic interneurons, disinhibiting pyramidal neurons and generating a net E/I imbalance (extension of the population model of E08, in the same line as A01 and A11). The progressive sensitization of the dopaminergic system to repeated stimuli favors a state of aberrant salience, in which neutral stimuli acquire excessive motivational relevance, a mechanism proposed to explain the formation of delusional ideas.

ID:4289